The present invention relates to ligands, transition metal complexes including such ligands and methods of using such ligands and complexes. More particularly the invention relates to ligands including first and second hetero atoms, transition metal complexes of such ligands in which only one of the first and second hetero atoms are directly bonded to the metal moiety and methods of using such ligands and complexes, for example, to facilitate chemical reactions, such as hydrolysis, alcoholysis and aminolysis reactions and carbon dioxide conversion reactions.
Medicinal chemists and biochemists want to know how amino acids are arranged in proteins, so that they can better understand the correlation between structures and the functions of drugs. One of the techniques used to accomplish the task of protein structure determination requires the breaking of amide bonds to liberate the amino acids. However, at physiological temperatures and pH 9, it takes an impractical length of time, for example, 168 years, to break half the amide bonds in a sample. In contrast, organisms found in nature have remarkably efficient systems to make and break amide bonds. Scientists have used natural enzymes such as carboxypeptidase to do the task of amide bond cleavage
In some cases it is believed the crucial step involves proton transfer between imidazole, a carboxylate, and the amide undergoing hydrolysis while other enzymatic systems involve a metal catalyzed amide bond cleavage such as that seen in the zinc(II)-metalloprotease. However, the available enzymatic systems can be very complicated and sometimes difficult to handle due to their sensitivity to temperature and pH.
Catalysis of amide hydrolysis has been catalyzed not only by enzymes, but also by acids, bases, and metal ions. These systems take advantage of one or more possible factors which facilitate amide bond cleavage. First, the amide bond cleaving reagent or catalyst could act as a proton transfer reagent which can be an important factor in amide bond hydrolysis. Secondly, a metal may catalyze or mediate amide hydrolysis by acting as a Lewis acid through O-complexation, delivery of a metal coordinated hydroxide or a combination of the latter two processes.
Considerable work has been directed toward studying the amide hydrolysis reaction and the development of reagents which assist amide hydrolysis. Some work toward the development of an amide hydrolysis catalyst has been published by Kostic. For example, Kostic and coworkers have found that a palladium(II) complex can accomplish the hydrolysis of a number of dipeptides, but with only a modest 4 catalytic turnovers.
It would be advantageous to provide reaction facilitators, e.g., catalysts, promoters and the like, that mimic enzymatic systems in their hydrogen-bonding and/or proton transfer abilities, but are robust, simple to handle, and have useful reactor facilitation.
Industrial hydrolysis of acrylonitrile is used to make acrylic acid which, in turn, can be converted to a variety of esters such as methyl, ethyl, butyl, and 2-ethylhexyl acrylates. The acrylates can then be used as comonomers with methyl methacrylate and/or vinyl acetate to give polymers for water-based paints, among other products A number of industrial methods exist for obtaining acrylic acids from nitriles and one of the more economical methods is the direct hydrolysis of the acrylonitrile to the acrylic acid. However, this synthetic route involves the use of a stoichiometric amount of sulfuric acid to produce the acrylamide sulfate which is then treated with an alcohol to give the acrylic ester. It would be advantageous to provide a direct route from the acrylonitrile and alcohol to yield the desired acrylate without the need to use and then neutralize a strong acid
As petroleum resources dwindle and the need to control the emissions of carbon dioxide into the environment increases, use of carbon dioxide as a feedstock becomes more desirable. It would be advantageous to provide materials useful to facilitate carbon dioxide conversion, for example, to carbonates, carbamates and ureas.
New ligands, transition metal complexes including such ligands and methods for using such ligands and complexes have been discovered. The present ligands and transition metal complexes can be produced using relatively straightforward synthetic chemistry techniques. Moreover, the structures of the present ligands and metal complexes can be effectively selected or even controlled, for example, in terms of proton transfer ability and/or hydrogen bonding ability, thereby providing ligands and complexes with properties effective to facilitate one or more chemical reactions. Thus, the present metal complexes can be effectively used to facilitate, for example, catalyze, promote and the like, various chemical reactions, such as hydrolysis, alcoholysis and aminolysis reactions and carbon dioxide conversion reactions, which provide useful benefits. The present ligands and complexes have one or more other advantageous properties or characteristics which enhance their production and/or usefulness.
In one broad aspect of the present invention, compositions are provided which comprise at least one organic ligand and a transition metal moiety partially complexed by the organic ligand.
The present organic ligands, many of which themselves are novel and within the scope of the invention, include a first hetero atom and a second hetero atom directly bonded to the first hetero atom or located one carbon atom away from the first hetero atom. When the present organic ligands are complexed to the transition metal moiety, only one of the first and second hetero atom is directly bonded to the transition metal moiety, with the other of the first and second hetero atoms not being directly bonded to another transition metal moiety or being directly bonded to H (hydrogen atom). In addition, in the event the first and second hetero atoms are nitrogen and are located in a heterocycle and the organic ligand includes only a single additional hetero atom separated from the first or second hetero atoms by one or two carbon atoms, then the additional hetero atom is not included in an additional heterocycle. Also, if the organic ligand includes more than four hetero atoms, then the organic ligand includes at least one hetero atom other than nitrogen bonded directly to two (or more) other atoms. Alternately, if the organic ligand includes two pyrazole rings and at least two hetero atoms in the group connecting the two rings, then the organic ligand includes at least one hetero atom other than nitrogen.
In another embodiment, compositions within the scope of the present invention include an organic ligand having the following structure: 
wherein the carbon atoms ortho to the nitrogen atoms in the two pendant heterocycles are bonded to a substituent other than xe2x80x94CH3 (methyl); and a transition metal moiety partially complexed by the organic ligand.
In an additional embodiment, the present compositions include an organic ligand having the following structure: 
The transition metal moiety partially complexed with this organic ligand preferably is other than ruthenium.
The present organic ligands can be very effectively structured and adapted to control the proton transfer ability and/or hydrogen bonding ability of the transition metal complex of which the ligand is a part. In other words, the present ligands can be selected to obtain the desired degree of proton transfer ability and/or hydrogen bonding ability so that the resulting transition metal complex is highly effective in the desired application, for example, in facilitating a particular or specific chemical reaction. Such adaptability is very useful in providing the proper or desired degree of proton transfer and/or hydrogen bonding to achieve the desired degree of facilitation of a number of important chemical reactions, for example, hydrolysis, alcoholysis and aminolysis reactions, carbon dioxide conversion reactions, and reactions of alkenes or alkynes with water, alcohols, ammonia or amines.
In another broad aspect of the present invention, methods for producing a hydrolysis product are provided. Such methods comprise contacting a hydrolysis reactant in the presence of a composition in accordance with the present invention in an amount effective to facilitate the hydrolysis of the hydrolysis reactant to the hydrolysis product. This contacting occurs at effective hydrolysis conditions.
In yet another broad aspect of the present invention, methods for producing an alcoholysis product are provided. Such methods comprise contacting an alcoholysis reactant in the presence of a composition in accordance with the present invention in an amount effective to facilitate the alcoholysis of the alcoholysis reactant to the alcoholysis product This contacting occurs at effective alcoholysis conditions.
In one other broad aspect of the present invention, methods for producing an aminolysis product are provided. Such methods comprise contacting an aminolysis reactant in the presence of a composition in accordance with the present invention in an amount effective to facilitate the aminolysis of the aminolysis reactant to the aminolysis product. This contacting occurs at effective aminolysis conditions.
In a further broad aspect of the present invention, methods for converting carbon dioxide are provided. Such methods comprise contacting carbon dioxide in the presence of a composition in accordance with the present invention in an amount effective to facilitate the conversion of the carbon dioxide to a conversion product. The contacting occurs at effective carbon dioxide conversion conditions. The conversion product preferably is selected from ureas, carbamates and carbonates.
In an additional broad aspect of the present invention, methods for reacting alkenes or alkynes with water, alcohols, ammonia or amines are provided. Such methods comprise contacting the reactants in the presence of a composition in accordance with the present invention in an amount effective to facilitate the desired reaction to one or more desired products. The contacting occurs at effective reaction conditions.
Each feature and combination of two or more features described herein are included within the scope of the present invention provided that any two features of any such combination are not mutually inconsistent or incompatible.
These and other aspects and advantages of the present invention are set forth in the following detailed description, examples and claims.
In one aspect, the present invention is directed to organic ligands including a first hetero atom and a second hetero atom directly bonded to the first hetero atom or located one carbon atom away from the first hetero atom Examples of hetero atoms include nitrogen atoms (N), oxygen atoms (O), sulfur atoms (S) and phosphorus atoms (P). At least one of the first and second hetero atoms is, preferably both the first and second hetero atoms are, nitrogen.
When the present organic ligands are complexed to the transition metal moiety, only one of the first and second hetero atoms is directly bonded to the transition metal moiety. The other of the first and second hetero atoms is not directly bonded to another transition metal moiety or is directly bonded to H (hydrogen atom). In the event both the first and second hetero atoms are nitrogen and are located in a heterocycle and the organic ligand includes only a single additional hetero atom separated from the first or second hetero atoms by one or two carbon atoms, then the additional hetero atom is not included in an additional heterocycle. Also, if the organic ligand includes more than four hetero atoms, then the organic ligand includes at least one hetero atom other than nitrogen bonded directly to two (or more) other atoms. Alternately, if the organic ligand includes two pyrazole rings and at least two hetero atoms in the group connecting the two rings, then the organic ligand includes at least one hetero atom other than nitrogen.
In one embodiment, the organic ligand includes a heterocycle, for example, including at least one or two carbon atoms, with both the first and second hetero atoms located in the heterocycle. The organic ligand may include a single additional hetero atom separated from the heterocycle by one or two carbon atoms. This single additional hetero atom preferably is not located in an additional heterocycle. The additional hetero atom preferably is bonded, that is directly bonded, to a carbon atom of the heterocycle.
In one very useful embodiment, the other of the first and second hetero atoms is directly bonded to H. The feature of the present invention enhances the opportunity of hydrogen bonding in the present transition metal complexes. More preferably, the other of the first and second hetero atoms is not directly bonded to another transition metal moiety and is directly bonded to H
The organic ligand may further include a third hetero atom located in a side chain bonded to the heterocycle including the first and second hetero atoms. The side chain may be bonded to the heterocycle at a carbon atom bonded directly to the first hetero atom. Alternately, the side chain may be bonded to one of the first and second hetero atoms. The side chain preferably includes one or two carbon atoms between the hererocycle and the third hetero atom.
One useful embodiment provides that the first and second hetero atoms are nitrogen atoms and the third hetero atom is selected from sulfur atoms, oxygen atoms and phosphorus atoms.
The organic ligands may include an additional heterocycle including one or two or more additional is hetero atoms. For example, the additional heterocycle may include a fourth hetero atom and a fifth hetero atom bonded to the fourth hetero atom or located one carbon atom away from the fourth hetero atom. The third hetero atom preferably is located in an additional side chain bonded to the additional heterocycle. Preferably, only one of the additional hetero atoms in the additional heterocycle, for example, only one of the fourth and fifth hetero atoms, is directly bonded to the transition metal moiety and the other additional hetero atom or atoms, for example, the other of the fourth and fifth hetero atoms, is (are) bonded directly to H.
Very useful organic ligands in accordance with the present invention are selected from the following: 
where n is an integer independently selected from one or two, and each R is independently selected from monovalent radicals, preferably monovalent substantially hydrocarbyl radicals.
Additionally, organic ligands in accordance with the present invention may be selected from: 
and all similar structures wherein the 
moiety is replaced by a 
moiety.
Still further, the present organic ligands may be selected from 
where L is selected from S, NH, NR, P, N, SR, PR and PR2, m is an integer selected from 1, 2 or 3 and each R is independently selected from monovalent radicals, preferably monovalent substantially hydrocarbyl radicals.
In another embodiment, the organic ligand has the following structure: 
wherein the carbon atoms ortho to the nitrogen atoms in the two pendant heterocycles are bonded to a substituent other than xe2x80x94CH3 (methyl).
In a still further embodiment, the organic ligand has the following structure: 
provided that the ligand is partially complexed to a transition metal moiety, as described elsewhere herein, other than a ruthenium moiety.
The transition metal moiety is partially complexed by at least one of the present organic ligands. The transition metal moiety may be a moiety of a metal selected from Group IB metals, Group IIB metals, Group IIIB metals, Group IVB metals, Group VB metals, Group VIB metals, Group VIIB metals and Group VIIIB metals. Preferably, the transition metal moiety is a moiety of a metal selected from chromium, manganese, iron, cobalt, nickel, copper, zinc, molybdenum, ruthenium, rhenium, palladium, silver, hafnium, tantalum, tungsten, rhodium, osmium, iridium, platinum and gold. Still more preferably, the transition metal moiety is a moiety of a metal selected from iron, cobalt, nickel, copper, zinc and palladium.
The present transition metal complexes preferably are soluble in the liquid medium in which such complexes are present or are used. The organic ligands may include one or more substituents, for example, one or more polar substituents and/or non-polar substituents, effective to increase the solubility of the ligand/transition metal complex in a given liquid medium. In addition, the present compositions may include one or more other or additional components, such as silver or thallium salts, acids, bases and the like, in an amount effective to interact with or otherwise affect the complex, for example, to activate the complex and/or to enhance the activity of the complex to facilitate a desired chemical reaction.
The present invention includes within its scope the present ligands and complexes as described herein and any and all substituted counterparts thereof. For example, unless otherwise expressly disclosed to the contrary, one or more of the hydrogen (H) substituents included in the present ligands can be replaced by another monovalent radical. Such substituted ligands, as well as the ligands with the hydrogen substituents, are included within the scope of the present invention.
In addition, any and all isomers, tautomers, enantiomers, and mixtures thereof of the present ligands are included within the scope of the present invention.
Examples of monovalent radicals which may be included as substituents in the present ligands, for example, as the R groups, include, but not limited to, monovalent hydrocarbon or hydrocarbyl groups, such as alkyl, alkenyl, alkynyl, aryl, alkyl aryl, alkenyl aryl, alkynyl aryl, aryl alkyl, aryl alkenyl, aryl alkynyl and cyclic monovalent hydrocarbon groups; halo such as F, Cl, Br and I; NH2; NO2; alkoxy; alkylthio; aryloxy; arylthio; alkanoyl; alkanoyloxy; aroyl; aroyloxy; acetyl; carbamoyl; alkylamino; dialkylamino; arylamino; alkylarylamino; diarylamino; alkanoylamino; alkylsulfinyl; alkylsulfenyl: alkylaulfonyl; alkylsulfonylamido; azido; benzyl; carboxy; cyano; guanyl; guanidino; imino; phosphinyl; silyl; thioxo; uredido or vinylidene or where one or more carbon atoms are replaced by one or more other species including, but not limited to, N, O, P, or S. The term xe2x80x9csubstantially hydrocarbyl radicalxe2x80x9d as used herein refers to a radical in which the number of carbon and hydrogen atoms are at least about 50%, and preferably at least about 70%, or at least about 80%, of the total number of atoms in the radical.
The present invention includes methods for producing a hydrolysis product. Such methods comprise contacting a hydrolysis reactant in the presence of a composition in accordance with the present invention in an amount effective to facilitate the hydrolysis of the hydrolysis reactant to the hydrolysis product. This contacting occurs at effective hydrolysis conditions. Such hydrolysis reaction conditions vary widely depending on many factors, such as the reactants and complex being employed, the concentrations of the reactants and complex, the desired product and other factors. However, such reaction conditions are not of critical importance in the present invention and may be selected from conditions conventionally used in similar reactions. Therefore, a detailed presentation of such conditions is not set forth herein.
The hydrolysis reactant preferably is selected from compounds including amide bonds, nitriles, phosphate esters, and cyanide ions.
Compounds including amide bonds which may be hydrolyzed in accordance with the present invention include, but are not limited to, formamide, acetamide, N-methylacetamide, N,N-dimethylacetamide, N,N-diethylacetamide, propionamide, N-methylpropionamide, is N,N-dimeethylpropionamide, N,N-diethylpropionamide, butyramide, N-methylbutyramide, N,N-dimethylbutyramide, acrylamide, N-methylacrylamide, N,N-dimethylacrylamide, benzamide, N-methylbenzamide, N,N-dimethylbenzamide, N,N-diethylbenzamide, o-, m-, and p-toluamides and their N-alkylated derivatives, acetanilide, o-, m-, and p-acetotoluidides, 2-acetamidophenol, 3-acetamidophenol, 4-acetamidophenol, N-acylated amino acids, glycylglycine, alanylalanine, and other polypeptides and proteins.
Nitriles which may be hydrolyzed in accordance with the present invention include, but are not limited to, linear or branched saturated alphatic C2-C18 mono- and C3-C19 dinitriles and phenyl derivatives thereof, C7-C13 saturated alphatic mono- and C5-C14 dinitriles, C3-C18 linear or branched olefinically unsaturated alphatic nitriles, C6-C13 olefinically unsaturated alicyclic nitriles, C7-C14 aromatic mono- and dinitriles C6-C8 heterocyclic nitrogen and oxygen mononitriles, C3-C4 cyanoalkanoic amides, C2-C12 saturated aliphatic cyanohydrins or hydroxynitriles, and mixtures of the above-described nitriles.
Specific examples include, but are not limited to, acetonitrile, propionitrile, buytronitrile, acrylonitrile, benzonitrile, and substituted derivatives Phosphate esters which may be hydrolyzed in accordance with the present invention include, but are not limited to, trialkyl phosphates, triaryl phosphates, dialkyl aryl phosphates, alkyl diaryl phosphates, dialkyl phosphates including DNA and RNA derivatives, diaryl phosphates, alkyl aryl phosphates, alkyl phosphates, aryl phosphates, and analogous phoshonic acid derivatives.
Further, the present invention includes methods for converting carbon dioxide. Such methods comprise contacting carbon dioxide in the presence of a composition in accordance with the present invention in an amount effective to facilitate the conversion of the carbon dioxide to a conversion product. The contacting occurs at effective carbon dioxide conversion conditions. Such reaction conditions vary widely depending on many factors, such as the complex being employed, concentrations of the carbon dioxide and complex, the desired product and other factors. However, such conditions are not critical in the present invention and may be selected from conditions conventionally utilized in similar carbon dioxide conversion reactions. Therefore, a detailed presentation of such conditions is not set forth here.
The carbon dioxide conversion product preferably is selected from ureas, carbamates and carbonates.
Another group of chemical reactions facilitated by the present metal complexes is illustrated by the reaction of alkenes with water to produce the corresponding alcohol.
Without wishing to limit the invention to any particular theory of operation, it is believed chat the reaction between water and ethylene can be facilitated using the present metal complexes in accordance with the mechanism given below: 
Similar reaction mechanisms can be envisioned for reactions of other alkenes or alkynes with water, alcohols, ammonia and amines These reactions are conducted by contacting the reactants together with the complex in accordance with the present invention at effective reaction conditions to obtain the desired product or products. Such reaction conditions can vary widely depending on many factors, such as the reactants and complex being employed, the concentrations of the reactants and complex, the desired product or products and other factors. However, such reaction conditions are not of critical importance in the present invention and may be selected from conditions conventionally used in similar reactions. Therefore, a detailed presentation of such conditions is not set forth here.
The present ligands can be produced from inexpensive and readily available materials, using chemical synthesis techniques which are well known in the art. To illustrate, many of the present ligands are derived from or based on pyrazole, and can be produced following one of two synthetic routes. In the first route pyrazole is converted to an electrophilic precursor, whereas in the second route the pyrazole precursor is the nucleophile.
Pyrazole 1 is converted into chloride 4 in accordance with the following reaction sequences: 
It has been found that an organic solvent is unnecessary in the first step or reaction and the yield of 2 exceeded 95%. Protected pyrazole 2 can then be lithiated with two equivalents of an alkyllithium, such as n-butyllithium, and the pyrazole moiety is than alkylated with formaldehyde. Subsequent deprotection in hydrochloric acid yielded 3. Alcohol 3 is then converted to chloride 4 with thionyl chloride, as noted above.
The present ligands can be prepared in accordance with the following: 
The desired ligand 5 can be obtained using three equivalents of lithium diphenylphosphide. Lithium thiomethoxide and sodium disulfide also can be used, giving ligands 6 and 7, respective1y. Further, this synthetic route gives access to mono-pyrazole ligands with the general structure of 5 and 6 (bis-pyrazole)-ligands, such as 7. By changing the R substituent and the tethered ligating atom, a library of ligands with varying steric hindrances and electronic environments can be produced. In addition, solubility properties of the resulting metal complexes can be drastically altered with the use of thiols, such as commercially available 2-mercaptoethanesulfonic acid sodium salt or 2-mercaptoethanol.
The pyrazole moiety as a carbon nucleophile can be used on electrophiles to obtain pyrazole-based ligands in a one pot synthesis. The Examples of such ligands include 9-11.

Isoelectronic and isosteric ligands can be prepared according to a synthetic route illustrated below: 
Compound 2 is converted to chloride 12, which can be used in the same way that isomer 4 is used. These ligands provide complexes not capable of hydrogen bonding when chelated to a metal through phosphorus and the unsubstituted nitrogen.
A range of transition metals with varying oxidation states can be complexed with the present ligands, for example, using the following general reaction scheme: 
In one embodiment, the metal has an oxidation state which is unlikely to give complexes which oxidatively add the nitrogen-hydrogen bond of the pyrazole moiety. In addition, the formation of stereoisomeric products preferably is reduced. The metals selected preferably are those likely to give four-coordinate complexes. A specific example is palladium(II).
In another embodiment, the oxidation state and structural criteria described above are retained and, in addition, the metals are selected based on a change in the relative pKa""s of their respective aquo-metal ions. Examples include metals such as platinum(II), zinc(II), and nickel(II), which have aquo-metal ions with pKa""s of 4, 9 and 10, respectively, whereas the aquo-metal ion of palladium(II) has a pKa of 2.
Metals capable of making hexa or penta coordinated complexes may be employed. Examples include chromium, manganese, iron, cobalt, copper, zinc, molybdenum, ruthenium, rhenium, palladium, silver hafnium, tantalum, tungsten, rhodium, osmium, iridium, platinum and gold. Still more preferably, the transition metal moiety is a moiety of a metal selected from iron, cobalt, copper, zinc and palladium.
The complexes can be substituted with various ligands such as triflate, acetate, water or alcohol. These changes in the metal complexes allow adjusting the solubilities of the complexes to enable the hydrolysis of amides, phosphodiesters and nitriles and the addition to carbon dioxide to be conducted in polar or nonpolar solvents.
The present complexes are effective as hydrolysis reagents or reaction facilitators, such as catalysts. For example, it has been found that the complex 19, set forth below: 
was catalytic toward the hydrolysis of N,N-dimethylacetamide and gave a more than 9% yield of the hydrolysis products. However, when complex 17 noted previously was used with dimethylformamide in acetonitrile and water at 75xc2x0 C. amide cleavage products in 4% yield were provided while complex 20 set forth below: 
was found to be inactive. Although these reactions were slow and only 2 catalytic turnovers were achieved, these results are preliminary in nature. The conditions for the hydrolysis can be adjusted to provide enhanced results.